Purpose:

Alveolar hemorrhage (AH) is an uncommon but oftentimes deadly severe manifestation of systemic lupus erythematosus (SLE). However, serologic and clinical predictors of SLE patients at increased risk of developing AH are not clear. Limited data from small case series suggest a link between AH and renal disease. This study uses a well-characterized, large, multi-ethnic, cross-sectional SLE cohort (n=2,448) to examine demographic, clinical and serologic associations with AH.

Method:

De-identified, electronic records of the SLE database were searched for patients with AH. Each case was matched with 4 SLE affected controls for age, sex, ethnicity and race, as well as compared to the entire remaining collection. Demographic, serologic and clinical characteristics were gathered from among 1,900 datapoints for each AH positive and AH negative SLE patient. Chi-square, McNemar's test and paired t-test were used for data analysis.

Results:

Among 2,448 SLE patients screened, 13 cases of well-documented AH were identified (10 females and 3 males). African race was more prevalent in AH patients than controls (23% vs. 8%, p=0.035). Patients with AH were younger at SLE diagnosis compared to controls [mean age at diagnosis 29.9 vs. 33.7 years (mean age difference 3.8 years, 95% CI 0.986.67, p=0.009)]. Of the ACR classification criteria for SLE, lupus nephritis as defined by presence of cellular casts was associated with AH (OR 4.75, 95% CI 1.5819.19, p=0.003); however, no association of AH with proteinuria was found (p=0.4). Even in this small cohort, AH was significantly associated with the presence of vasculitis at other sites (OR 3.25, 95% CI 1.0013.68, p=0.05). Although no significant relation with clinically manifest antiphospholipid (aPL) syndrome was shown (p=0.55), aPL antibodies were more common in patients with AH (OR 3.17 with 95% CI 1.229.69, p=0.016). On the contrary, anti-Sm was significantly more prevalent in patients without AH in this cohort (OR <0.01 with 95% CI 0.000.69, p=0.023). The prevalence of other auto-antibodies, including anti-dsDNA, anti-Ro, anti-La and anti-nRNP, did not differ significantly in patients with and without AH.

Conclusion:

Clinical association of AH with vasculitis at other sites, as well as with the presence of cellular casts, suggests a possible common autoimmune pathway that leads to multicentric, microvascular involvement in the lung, glomerulus and other organs. Association of AH with aPL antibodies supports a presumed pathogenic mechanism that leads to AH through formation of miscovascular thrombi, with or without pulmonary capillaritis. Replication and expansion of these findings in additional longitudinal cohorts of SLE patients is warranted, as well as expanded evaluation of potential serologic predictors of this oftentimes severe clinical manifestation.